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Choriocarcinoma (CC) is a malignant trophoblastic tumor that occurs in women of childbearing age. Its cure rate could be over 90% following single drug or multidrug chemotherapy with methotrexate, 5-fluorouracil and etc. Chemoresistance is the main cause of treatment failure in CC, and the mechanisms have yet to be elucidated. Most of the previous works on the chemoresistance of CC focused on the transcript and protein levels, and much less attention was put on the metabolic level. In this study, the metabolomic phenotypes of two lines of CC cell, methotrexate-resistant cell (JEG3R) and methotrexate-sensitive cell (JEG3), as well as the medium extracts, were investigated using an NMR-based metabonomics method. The results showed that the chemoresistance of CC was likely related to disturbed glucose metabolism. Glucitol accumulation was observed only in the JEG3R cell line, suggesting the involvement of aldose reductase in the development of chemoresistance. In addition, methotrexate chemoresistance was also associated with lactate accumulation and stimulated alanine synthesis to fuel the Krebs cycle. The levels of amino acids, nucleotides and phosphocholine in the resistant line showed significant differences from the non-resistant line, and positive correlations with the proliferation rate of CC. This study provided insights into the chemoresistance of CC from the metabolism aspect.

Gut microbiota is important for human health. The complex relationship between intestinal flora and bile acid profile has been studied previously. However, few previous studies have determined the profile and functions of bile acids in different intestinal segments, and whether they are related to the distribution of intestinal flora. In this paper, we measured the distribution of bile acids in different intestinal segments of male and female C57BL/6 mice with ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-QqQ-MS) based targeted metabonomics analysis and nuclear magnetic resonance (NMR) based untargeted metabonomics analysis. Gender difference in distributions of bile acids were observed, which was more evident in the lower parts of intestine than in the upper part of intestine, especially in the cecum segment. This might be related to the abundance of gut microflora in different intestine segments. This study provided metabolic phenotypes of bile acids in mice of different genders, and demonstrated their interactions with gut microbiota.

The combination of doxorubicin and paclitaxel is widely used in clinical cancer therapy. Due to enhanced permeation and retention effects of nanomaterials in tumor tissues, nanocarriers with good biocompatibility have been designed to encapsulate doxorubicin/paclitaxel, and used to facilitate delivery of the drugs to achieve better therapeutic outcome. In this study, NMR-based metabonomic analyses were used to study the metabolic profiles in spleen tissues of normal healthy mice and of 4T1 tumor-bearing mice, which were treated with either saline, or doxorubicin/paclitaxel in their free forms, or doxorubicin/paclitaxel encapsulated in nanocarriers. The results demonstrated that treatment with the free forms of doxorubicin/paclitaxel remitted tumor-induced disturbances in gut microbiota, while treatment with nanocarrier-encapsulated doxorubicin/paclitaxel alleviated increased glucose and fumarate metabolism associated with tumor bearing. In contrast, tumor-related splenomegaly and metabolic alterations in amino acids, organic acids, nucleic acids and choline, both attributable to immune responses of the spleen, were not ameliorated by drug treatment. This could also be due to the fact that the treatment period was too short to have any significant effects. This work provided metabolic phenotypical information of the spleen tissues in 4T1 tumor-bearing mice, and helped to understand the metabolic impacts of drug delivery systems on the spleen.

Objective * To determine the half-life and half-lethal dose of itaconic acid in mice, and provide intuitive data for the metabolic rate and toxicity of itaconic acid in mice. Methods * Itaconic acid was injected into mice through caudal vein. The concentration of itaconic acid was measured by blood collection under fundus venous plexus at different time. At the same time, the survival of the mice was recorded after injection for 14 d. Results * Under the conditions of this experiment, the half-life of itaconic acid in male C57BL/6J mice was 29.13 min, and the half-lethal dose of is 258.263 mg/kg. Conclusion * Itaconic acid has a fast metabolic rate and a short half-life in mice. Itaconic acid is less toxic, based on its half-lethal dose in mice. [ABSTRACT FROM AUTHOR]

Objective: Using cone beam computed tomography (CBCT) in image measurement on the patients with maxillary protrusion, the study aims to identify the changes in root and alveolar bone before and after treatment by upper incisor retraction., Methods: The study was conducted on 37 patients who have received orthodontic treatment from January 2014 to December 2015. The sample comprised 17 males and 20 females, with an average age of 14.5 years. The patients underwent extraction of bimaxillary premolars and given maximum anchorage to retract the upper incisors. The adducent angle, adducent amount, and the amount of elongation of the upper incisor teeth were measured by cephalograms. The patients were scanned by NewTom VGi to obtain CBCT data before and after treatment with upper incisor retraction. Using the NewTom NNT tool, we obtained the multiple planar reconstruction and then adjusted the coronal, axial, and sagittal axis. The sagittal section of the long axis of the maxillary central incisor through the incisal edge and root apex was selected to measure the changes in the root and alveolar bone before and after incisional treatment., Results: Before and after retracting the upper incisors, the adducent angle of central incisor measured 12.92°±6.43°. Adducent amount of the incisors reached (5.54±2.21) mm. Incisor extension amount totaled (0.60±0.95) mm. Root absorption length was (0.81±0.46) mm. Root absorption rate was 6.80%±3.60%. Statistical differences were observed in the changes in root length before and after incisor retraction (P<0.05). After upper incisor retraction, increasing distance from the labial side alveolar ridge to the cemento-enamel junction reached (0.20±0.22) mm. After treatment, we observed that the height of the labial-side alveolar bones decreased and showed statistical difference with the height of labialside alveolar bones before treatment (P<0.05). The results show the correlation between root absorption and horizontal displacement of maxillary center incisor and the distance from the upper incisor apex to labial cortical bone. A correlation also exists between the variable quantity of the labial-side alveolar bones and adducent angle of the upper incisor, with a correlation coefficient of 0.354. The results also show significant difference (P<0.05)., Conclusions: After compensatory treatment of patients with maxillary protrusion, the root length of upper incisor was absorbed remarkably. The height of the labial-side alveolar bones was reduced. A greater tooth movement or beyond the anatomical limitations and alteration limits of the alveolar bone can easily lead to root resorption. A negative correlation exists between the variable quantity of the labialside alveolar bones and adducent angle of the upper incisor.

Objective: To investigate the effect of Colquhounia root tablet on IL-2 and IFN-γ mRNA expression in experimental allergic encephalomyelitis (EAE) of rats., Methods: The allergic encephalomyelitis model was established in Wistar rats by immunization with myelin basic protein of spinal cord of guinea pig and complete Freund's adjuvant. The rats in treatment group received Colquhounia root tablet (300 mg*kg(-1), BID). The symptom of EAE was observed; pathological feature and myelin of brain and spinal cord were detected with HE stain and Loyez's stain, respectively. The expressions of IL-2 and IFN-γ mRNA were assayed by RT-PCR., Results: No EAE symptoms were developed in treatment group, the expressions of IL-2 and IFN-γ mRNA were 0.345 ± 0.032 and 0.353 ± 0.023, which were significantly lower than those of model group (P<0.01). The histopathologic examinations revealed that less inflammation cells around vessels and demyelination in white matter of brain and spinal cords were observed in treatment group than in model group., Conclusion: Colquhounia root tablets are effective in treatment of EAE of rats, which may be associated with inhibition of the expression of IL-2 and IFN-γ mRNA.

Objective: To explore prognostic factors and the expression of glypican-3, hepatocyte antigen (HEP), alpha-fetoprotein (AFP), CD34 and CD10 in hepatocellular carcinoma (HCC) and their prognostic value., Methods: Clinicopathologic data were analyzed in 375 cases of HCC, in which 80 cases with follow-up were examined by immunohistochemical staining to detect the expression of glypican-3, HEP, AFP, CD34 and CD10 proteins. The relationship between the proteins expression and clinicopathologic features was also evaluated., Results: Tumor number (P = 0.000), tumor size (P = 0.025), tumor differentiation (P = 0.001) and vessel invasion (P = 0.000) were closely related to prognosis of HCC patients; the expression of glypican-3 (66/80,82.5%; P = 0.002), HEP (64/80,80.0%; P = 0.021), AFP (38/80,47.5%; P = 0.014) and CD10 (28/80,35.0%; P = 0.002) was significantly related to tumor differentiation; that of glypican-3 was significantly correlated with tumor number and presence of satellite nodules (P = 0.028) and that of AFP and CD10 was significantly correlated with portal vein thrombi (P = 0.000, P = 0.010). On Kaplan-Meier regression analysis, both low expression of HEP and high expression of AFP were closely related to poor prognosis., Conclusions: Tumor number, size, differentiation and vessel invasion were important factors affecting the prognosis of patients with HCC. HEP and AFP have prognostic significance in HCC.

Objective: To study the expression and significance of GPC3, CD10 and CD34 in hepatocellular carcinoma (HCC), dysplastic nodules (DN), cirrhotic regenerative nodules (CRN), focal nodular hyperplasia (FNH) and hepatocellular adenoma (HA)., Methods: Immunohistochemical study for GPC3, CD10, CD34 and AFP was performed on 80 cases of HCC (30 cases of well-differentiated HCC and 50 cases of advanced HCC), 30 cases of DN (18 cases of high-grade DN and 12 cases of low-grade DN), 36 cases of CRN, 20 cases of FNH and 20 cases of HA., Results: (1) The positive expression rate of GPC3 was 92% (46/50) in advanced HCC, 66.7% (20/30) in well-differentiated HCC, 2/18 in high-grade DN, and 0 in low-grade DN, CRN, FNH and HA. The expression rate of GPC3 in well-differentiated HCC was lower than that in advanced HCC and higher than that in high-grade DN (P < 0.05). (2) The negative expression rate of CD10 was 78% (39/50) in advanced HCC, 43.3% (13/30) in well-differentiated HCC, 20% (4/20 and 4/20) in both FNH and HA, 2.8% (1/36) in CRN and 0 in both high-grade DN and low-grade DN. The occurrence of CD10-strongly positive cells was 2% (1/50) in advanced HCC, 16.7% (5/30) in well-differentiated HCC, 15/18 in high-grade DN, 11/12 in low-grade DN, 80.6% (29/36) in CRN and 60% (12/20 and 12/20) in both FNH and HA. The positive expression rate of CD10 in well-differentiated HCC was higher than that in advanced HCC and lower than that in high-grade DN, low-grade DN, CRN, FNH and HA (P < 0.05). (3) The positive expression rates of CD34 in advanced HCC and well-differentiated HCC ranged from 25% to 100% [and strongly positive in 76% (38/50) and 70% (21/30), respectively]. The rates in high-grade DN and low-grade DN ranged from 5% to 25% (and weakly positive in 16/18 and 10/12, respectively). In CRN, the rate ranged from 0 to 5% [and weakly positive in 27.8% (10/36)]. In FNH and HA, the positive rates ranged from 25% to 50%. The positive expression rate of CD34 in well-differentiated HCC was significantly higher than that in high-grade DN, low-grade DN, CRN, FNH and HA (P < 0.05). (4) The positive expression rate of AFP was 44% (22/50) in advanced HCC, 20% (6/30) in well-differentiated HCC, no expression in DN, LCN, LCN, FNH and HA. The positive expression rate of AFP in well-differentiated HCC was lower than that in advanced HCC and higher than that in LCN, FNH and HA. The different expression had statistical significance (P < 0.05)., Conclusions: GPC3 is a relatively sensitive and specific marker in pathologic diagnosis of HCC. When coupled with immunohistochemical results of CD34, CD10 and AFP, GPC3 is useful in differentiating HCC from DN, LCN, FNH and HA.

Objective: To analyze the clinicopathologic features and prognostic factors of hepatocellular carcinoma., Methods: Clinicopathological data of 185 cases of hepatocellular carcinoma treated in our hospital between 2000 and 2005 were collected and their follow up information was obtained. The clinicopathological features and prognostic factors were analyzed by Kaplan-Meier and multivariate Cox regression analysis., Results: The 185 patients had a median age of 51.0 ± 11.0 (range, 19 - 72) years. The apparent peak incidence age was 40 to 60 years old, and the ratio of male to female was 10.6:1; the 3- and 5-year postoperational survival rates were 52.0% and 38.0%; respectively. The tumour numbers (P = 0.000), tumor size (P = 0.025), histological pattern (P = 0.000), nuclear features (P = 0.000), differentiation (P = 0.001) and vascular invasion (P = 0.000) were significantly correlated with prognosis. The postoperational survival times of patients with thin trabeculae pattern, compact pattern and pseudoglandular pattern were significantly longer than that of thick trabeculae, scirrhous pattern, and solid pattern (P ≤ 0.009). The postoperational survival time of patients with nuclear features grade 1 and 2 was significantly longer than that of grade 3 and 4 (P = 0.000). Multivariate Cox regression analysis showed that the tumor number (P = 0.001), tumor size (P = 0.042), nuclear features (P = 0.023) and vascular invasion (P = 0.000) were independent prognostic factors., Conclusion: The postoperational survival rate of HCC patients is low. The tumor size, tumor number, differentiation and vascular invasion are major prognostic factors of hepatocellular carcinoma, The higher is the tumor number, tumor size, degree of differentiation and presence of vascular invasion, the higher risk of mortality is.

Objectives: To evaluate the relationship between the functional integrity of sperm membrane and seminal parameters related to CASA., Methods: Thirty-eight fertile and one hundrend and twenty four infertile males were tested the functional integrity of sperm membrane by the kit and parameters by CASA., Results: There was a significant difference in the functional integrity of sperm membrane between fertile and infertile group (P < 0.01). The items related to CASA between normal and abnormal group in the functional integrity of sperm membrane had a remarkable difference, except motion degree, seminal volume and pH., Conclusions: To determine the functional integrity of sperm membrane can be used as a necessary supplementary method for CASA, and it has clinical significance in diagnosing, treating and researching male infertility.